The invention relates to a method for sterilizing an implantable sensor and to a sterilizing device for sterilizing an implantable sensor. The sensor serves for sensing at least one analyte in a body tissue. The sensor may particularly be an electrochemical sensor, which is set up for qualitatively and/or quantitatively sensing one or more analytes in a body tissue by electrochemical means. Such sensors are used, for example, in the monitoring of blood glucose concentrations. Other areas of use are also conceivable.
The prior art discloses a large number of sensors which can be completely or partially implanted in a body tissue and which serve for monitoring certain bodily functions, in particular for monitoring one or more concentrations of certain analytes. Without restricting further possible configurations, the invention is described hereinafter with reference to a blood glucose monitoring device. In principle, however, the invention can also be transferred to other types of analytes.
In addition to so-called point measurements, in which a sample of a bodily fluid is taken from a user in a targeted fashion and investigated for the analyte concentration, continuous measurements are also increasingly becoming established. Thus, for example, in the recent past a continuous glucose measurement in the interstitium, which is also referred to as continuous monitoring, CM, has become established as an important method for managing, monitoring and controlling a diabetes status. Directly implantable electrochemical sensors, which are often also referred to as needle-type sensors (NTS), are generally used for this. In this case, the active sensor region is brought directly up to the measuring site, which is generally arranged in the interstitial tissue, and glucose is converted into electrical current, for example using an enzyme, for example glucose oxidase, where the current is in proportion to the glucose concentration and can be used as a measured variable. Examples of such transcutaneous measuring systems are described in U.S. Pat. No. 6,360,888 B1 and in US 2008/0242962 A1.
Present-day continuous monitoring systems are consequently generally transcutaneous systems. This means that the actual sensor part of the sensor with the electrodes is arranged under the user's skin in a body tissue. An electronics part, which is often also referred to as the evaluation and/or control part or else as the patch, is generally located outside the user's body however, that is to say outside the human or animal body. The sensor part is in this case generally applied by means of an insertion aid, which is likewise described by way of example in U.S. Pat. No. 6,360,888 B1. Other types of insertion aids are also known. The time for which a sensor is worn is generally about 1 week.
Complete or partial insertion of the sensor into a body tissue generally requires that completely or partially implantable components of the sensor must be sterilized in accordance with existing standards for use on a human and/or animal. In the case of enzymatically based electrochemical glucose sensors, the enzyme is directly embedded in the electrode or in contact with the interstitium via a protective layer, i.e. the electrodes are exposed. Chemical or thermal sterilization is accordingly generally ruled out, since in the case of such forms of sterilization the enzyme of the electrodes would be damaged. Therefore, generally only radiation sterilization can be used.
Here, however, there is the problem that electronic components of the sensor generally do not withstand direct exposure to radiation, for example to beta radiation or electron radiation, at the radiation doses that are typically necessary (usually 25 kGy). Particular, semiconductor-based active electronic components, such as for example high-impedance amplifier components or potentiostats, are not usually capable of withstanding radiation sterilizations with beta radiation at the radiation doses mentioned without suffering losses in function.
The prior art discloses a large number of methods by means of which protection of sensor elements during radiation sterilization can take place. Thus, for example, a method for producing integrated, diagnostic test elements is described in WO 2006/005503 A1. The test elements have a puncture region and a detection region. The detection region on the test element is shielded from electron radiation that is used for the sterilization. It is also described, inter alia, that the test elements may be arranged in a package, and that the package may be designed such that the detection region of the test elements is shielded from electron radiation and that irradiation of the entire package is performed.
In U.S. Pat. No. 5,496,302 there is described a method for sterilizing a selected region of a product and for producing a sterile product from two or more components that cannot be sterilized in the same way. This involves using a system of tubes with a sterile fluid, in which one part of a housing is sterilized with electron radiation, while another part is protected from the effects of the electron beams by a shielding.
In US 2008/0255440 A1 there is described a sensor package with an implantable sensor. The implantable sensor has an electrode region and an electrical contact region. The sensor is sterilized by beta rays, the package being designed in such a way that the electrical contact region is sterilized, whereas the electrode region remains protected. The package may, for example, protect a sensor part from the influence of further gases that are used for sterilizing electronic components.
In U.S. Pat. No. 6,594,156 B1 there is described a device for protecting electrical circuits during high-energy radiation sterilization. The device comprises a carrier substrate and a protective housing for electronic components. The protective housing is hermetically coupled to the carrier substrate of the electronic components and protects them from the effects of the radiation sterilization. Also described are electronic circuits which are sterilized with a predetermined radiation dose and in which, after the sterilization, the gain factor is not reduced beyond a certain amount and the proportionality between the collector current and the base current is retained.
The solutions known from the prior art have many technical challenges and even disadvantages. Thus, the known solutions are generally not set up for sterilizing a sensor or a sensor system that can be used on a human body without further complex steps. In particular, it is generally not taken into consideration that such a sensor system has parts coming into contact with the skin which on the one hand must be sterile but on the other hand must be in direct contact with the sensitive electronics. In order that the sensor system is sterilized to the entire extent that is necessary, with known devices and methods a number of successive sterilizing methods are often used, such as for example radiation sterilization and chemical sterilization.
Furthermore, the devices known from the prior art are often of such a complex design that they are virtually unusable in industrial processes. Thus, before and after the radiation sterilization, complex preparation or subsequent treatment of the sterilizing device is generally required, during which re-contamination of the sensors may take place. At the same time, however, the sterilizing devices are so complex that they generally could not be delivered to a final customer as a complete unit, together with the shielding device.